Non-invasive techniques for medical use are of great interest, for example for glucose monitoring for diabetics, where devices for portable self monitoring are important. A great deal of research and development effort has gone into this area. In recent years a number of new sensor technologies have been explored, including transdermal sensing.
Transdermal sensing uses a sensor that is positioned on a patient's skin to sense substances, for example in the blood stream or in the interstitial fluid, through the skin. Transdermal extraction of molecules can be done using microneedles, but this involves piercing the skin, which gives opportunity for infection and/or needle breakage. Alternatively, ultrasound can be used to permeate the skin. However, this requires a more complex device, and skin is highly permeable for a short timeafterwards.
Transdermal methods which do not breach the skin or can measure through the epidermis are appealing. One such method is iontophoresis. Iontophoresis involves using a low electric current typically passed through gel electrodes to introduce ions of a medicine into tissue. This has been used for transdermal drug delivery and local anaesthetics. Reverse Iontophoresis (RI) is the term for the use of iontophoresis to extract molecules from the skin for diagnostics. RI is based on the same principle of low current passing through gel electrodes into the skin, but instead of delivery, there is an extraction of charged and uncharged molecules and ions into the gel for detection.
WO86/04680A1 describes a patch that has a moist or liquid bridge on the skin to let molecules diffuse into a material that binds the molecules. From time to time the complete system is removed from the skin and the bridge material treated or tested. The device collects an amount of the molecule of interest depending on the permeability of the skin at that time, the time of application of the patch and the starting quantities of the molecule already present in the sweat pores or on the skin. A problem with the device of WO86/04680 is that the liquid bridge suggested would not allow the amount of analyte of interest in the bridge to be instantly or continuously monitored.
WO00/057177 describes a patch that combines an outer membrane with a hydrophobic liquid bridge that is in contact with the skin to allow diffusion of an analyte, for example glucose, to the membrane. The membrane has a colour change chemistry system that reacts with the analyte in the membrane and changes colour. Thus, a glucose reading can be obtained by placing the patch on the skin, waiting and then reading the colour change on the membrane. A problem with this system is that skin bound glucose and sweat pore glucose are included in the reading and only the overall colour change related to the time period of contact of the material with the skin and the skin's permeability is provided. Thus, temporal fluctuations cannot be detected. Another problem is that the device cannot be used to continuously measure the analyte.
WO2009/025698 describes devices for collecting and analysing sweat using a sweat collection device. This has a gradient and a collection location. The gradient is configured to direct sweat toward the collection location when the sweat collection device is applied to a skin surface. This gradient is a surface energy or radial gradient that can be designed to enhance and guide the flow of sweat. The gradient is created by hydrophobic and hydrophilic patterns and guides the sweat preferentially along the hydrophilic areas. The device is dependent on sweat generation and flow and thus dependent on physiological activity or induced sweating to detect a glucose or analyte level of sweat. This is difficult to apply in practice to temporal monitoring of analyte without multiple changes of the skin patch. It is also difficult in practice to separate transdermal diffusion of analyte from sweat borne analyte for many molecules.